Immunotherapy With Y90-RadioEmbolization for Metastatic Colorectal Cancer

Inclusion Criteria: * Age ≥18 years * Histological or cytological confirmation of colorectal cancer with metastasis to the liver. Mismatch repair or microsatellite instability status of the tumor needs to be known. Tumors need to be mismatch repair proficient (for mismatch repair deficient tumors immunotherapy is already approved). * Patient must have at least 1 liver lesion measurable as defined in the protocol * Must have liver metastases and be appropriate for treatment with Y-90 radioembolization therapy as determined by the treating medical oncologist and interventional radiologist/oncologist, and nuclear medicine physician(s). NOTE: the goal of therapy is safety and parenchymal sparing. Typically, since the treatment is personalized, the goal is to have at least 30% liver parenchymal sparing post treatment. * Must have a metastatic focus amendable to biopsy. It is permissible to use same or alternative lesion for biopsy for assessment for tumor response and changes in microenvironment (mandatory pre- and post-Y90-RE biopsy). * At least 2 but no more than 3 lines of therapy allowed in metastatic setting. These include at least treatment with a fluoropyrimidine, oxaliplatin, and/or irinotecan-based therapy, an anti-VEGF therapy and, if RAS wild-type, an anti-EGFR therapy, unless deemed intolerant or not suitable by the treating oncologist. NOTE: adjuvant and/or maintenance chemotherapy does not count as an additional line of therapy. (Patients with more than 3 lines of therapy are at risk for liver disease from prior systemic therapies and would not be reasonable candidates for Y90-RE). * ECOG Performance Status (PS) 0 or 1. * Negative serum pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only. * Females of childbearing potential (FOCBP), must use appropriate method(s) of contraception. FOCBP are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Additionally, FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with durvalumab plus 5 half-lives of durvalumab (13 weeks) plus 30 days (duration of ovulatory cycle) for a total of 17 weeks post-treatment completion (details in appendix). * Men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with durvalumab plus 5 half-lives of durvalumab plus 90 days (duration of sperm turnover) for a total of 25 weeks post-treatment completion (details in appendix). * Provide written informed consent. * Ability to complete questionnaire(s) by themselves or with assistance. * Willingness to provide mandatory blood specimens for correlative research (detailed in protocol). * Willingness to provide mandatory tissue specimens for correlative research (detailed in protocol). NOTE: If tissue is deemed inaccessible, patient cannot participate in study. * Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study). * Must have a life expectancy of at least 6 months. Exclusion Criteria: * Any of the following laboratory abnormalities: * Hemoglobin \<8.0 g/dL * Absolute neutrophil count (ANC) \<1500/mm3 * Platelet count \<100,000/mm3 * Total bilirubin \>1.5 x ULN (except in subjects with Gilbert Syndrome, who cannot have a total bilirubin \> 3.0 mg/dL) * Alanine aminotransferase (ALT) and Aspartate transaminase (AST) \>2.5 x ULN * Serum creatinine \> 1.5 x ULN OR * Calculated creatinine clearance \<30 ml/min using the Cockcroft-Gault formula * Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: * Pregnant persons * Nursing persons * Persons of childbearing potential who are unwilling to employ adequate contraception * Co-morbid systemic infections, or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. * Untreated central nervous system (CNS) metastatic disease (including spinal cord and leptomeningeal disease). NOTE: Patients with previously treated CNS metastases that are radiographically and neurologically stable for ≥ 6 weeks are permitted. * Uncontrolled intercurrent illness including, but not limited to, autoimmune disease, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. EXCEPTION: Patients who have adequately controlled autoimmune disease with or without medications are permitted as long as deemed reasonable by treating physician. * Received any other investigational agent incorporating chemotherapy and/or biologics within 14 days prior to first dose of durvalumab which would be considered as a treatment for the primary neoplasm. For patients on active treatment, last treatment and 1st dose of Durvalumab should be at least ≥ 14 days. EXCEPTION: Other forms of concurrent observational studies are permitted. * Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Non-melanoma skin cancer, lentigo maligna- in-situ, or carcinoma-in-situ of the cervix. Also prior malignancy already treated with curative intent and with no known active disease present would be considered eligible. * History of unstable cardiac disease defined as one of the following: * Congestive heart failure \> class II New York Heart Association (NYHA). (Appendix II) * Unstable angina (angina symptoms at rest) or new onset angina (began ≤ 3 months prior to registration) * Myocardial infarction ≤ 3 months * Uncontrolled cardiac ventricular arrhythmias. EXCEPTION: Subjects that are stable on anti-arrhythmic therapy are eligible. * Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment within 14 days of first dose of durvalumab. NOTE: Subjects can be screened during washout period. * History of severe allergic reactions (i.e. Grade 4 allergy, anaphylactic reaction from which the subject did not recover ≤ 6 hours of initiation of supportive care) * Failure to recover from toxicities from prior anti-cancer therapy, defined as having not resolved to National Cancer Institute (NCI) CTCAE version 5.0 Grade ≤ 1. EXCEPTIONS: Alopecia and laboratory values listed per the exclusion criteria. Also subjects with irreversible toxicity that is not reasonably expected to be exacerbated by any investigational products (i.e. hearing loss) will be permitted. * Use of steroids. EXCEPTIONS: Systemic glucocorticoids will be permitted as long as it is ≤20 mg of prednisone equivalent. Topical steroids, such as bronchodilators and local steroid injections are also permitted if clinically required. * Patients with renal failure currently requiring dialysis of any kind. * Patients weighing \<30kg will be excluded from enrollment * History of allogenic organ transplantation