A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC

Inclusion Criteria: * Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age ≥ 18 years at the time of consent. * ECOG Performance Status of ≤ 2 and/or sufficient to undergo both perioperative systemic chemotherapy and hepatic surgery as determined by surgical and medical oncology evaluations. * Histologically confirmed hepatic-limited metastatic colorectal cancer. * Genomic testing results are required. FoundationOne platform is preferred, however results from an equivalent genomic platform may be used after discussion with the sponsor investigator. * Completely resectable disease as determined by the guidelines below and surgical oncology evaluation. Patients with bilobar disease that requires resection and ablation are allowed provided the surgical oncologist can render the patient NED (no evidence of disease) at the conclusion of the operation. Synchronous primary colorectal and metastatic hepatic tumors are eligible, provided all disease can be resected in a single operation. NOTE: Subjects who had surgery for their primary tumor prior to registration to this trial are still eligible. Additionally: * No radiographic evidence of involvement of: extrahepatic bile ducts, main portal vein or celiac/retroperitoneal lymph nodes. * Adequate predicted functional liver remnant (FLR) as deemed by the individual site surgical oncologists. * Patients with synchronous metastatic disease are allowed provided their primary tumor can be completely resected at the time of metastasectomy. Neoadjuvant pelvic radiotherapy for rectal cancer is not permitted * Patients must be treatment naïve with respect to their stage IV colorectal cancer. History of prior adjuvant systemic chemotherapy containing oxaliplatin is allowed as long as as it has been greater than 12 months from completion of oxaliplatin to study enrollment. NOTE: Neoadjuvant pelvic chemoradiotherapy as part of the management of synchronous metastatic rectal cancer is allowed, provided chemoradiation was completed prior to enrollment on study. * Hematological: * Platelet Count ≥ 100,000 mm\^3 * Absolute Neutrophil Count (ANC) ≥1500 µ/L * Hemoglobin (Hgb) ≥ 9 g/dL * Renal: o Creatinine \< 1.5 x ULN OR Calculated Creatinine Clearance ≥ 60 mL/min * Hepatic: * Total Bilirubin ≤ 1.5 × upper limit of normal (ULN)\^2 * Aspartate aminotransferase (AST) ≤ 5 × ULN; given presence of liver metastases * Alanine aminotransferase (ALT) ≤ 5 × ULN; given presence of liver metastases * Alkaline Phosphatase \< 2.5 x ULN * INR, PT, or APTT ≤ 1.5x ULN unless participant is receiving anticoagulant therapy, in which case they must be on a stable dose * Females of childbearing potential must have a negative serum pregnancy test within 24 hours of study drug. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months without another cause, or a documented serum follicle stimulating hormone (FSH) ≥ 35 mIU/mL. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Females of childbearing potential and male participants must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol. * As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. Exclusion Criteria: * Patients with mutations in or deficient expression of one or more of the mismatch repair genes listed: MSH2, MSH3, MSH6, MLH1, PMS1, PMS2. * Active infection requiring systemic therapy. * Pregnant or breastfeeding. * Second primary malignancy. Clear exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 3 years and, 2) in situ carcinoma (e.g. in situ carcinoma of the cervix). Patients with chronic lymphocytic leukemia will be allowed if their blood counts are within acceptable hematologic parameters and if they are not currently requiring cytotoxic or biologic anticancer treatment (supportive treatment such as IVIG is permitted). * Metastatic disease not limited to the liver. * Disease not amenable to complete resection, not resectable within the confines of a single surgery, or where resection would result in inadequate functional liver remnant. * Prior surgery or systemic therapy for colorectal cancer within 6 months or 12 months if systemic chemotherapy included oxaliplatin of study enrollment. * Immunodeficient patients including but not limited to patients with HIV/AIDS and chronic Hepatitis B and C. * Patient with clinically significant cardiomyopathy, coronary disease, heart failure New York Heart Association (NYHA) class III or IV, or cerebrovascular accident (CVA) within 1 year of study enrollment (CV301). * Subjects with known severe allergy to eggs, egg products, or aminoglycoside antibiotics (for example, gentamicin or tobramycin) (CV301). * Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. * Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. * Participants with history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (e.g. Hormone replacement after adrenal crisis) * Excluding patients with serious or uncontrolled medical disorders * Treatment with botanical preparations (e.g. herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization/treatment. * History of allergy or hypersensitivity to study drug components. * History of allogenic stem cell or solid organ transplant.