Safety Study of Regorafenib and SIR-Spheres® Microspheres Radioembolization in Patients With Refractory Metastatic Colorectal Cancer With Liver Metastases

Inclusion Criteria: 1. Histologically confirmed metastatic adenocarcinoma of the colon or rectum. 2. Patients who have been previously treated with or are not candidates for fluorouracil, oxaliplatin, irinotecan, and if Kras wild-type, anti EGFR therapy. 3. Considered an appropriate candidate for regorafenib therapy. 4. Measurable disease or evaluable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 5. Measurable computed tomography (CT) scan evidence of liver metastases which are not treatable by surgical resection or local ablation with curative intent at the time of study entry. 6. ECOG Performance Status score of 0-1. 7. Adequate hematologic, renal and liver function. 8. Male patients with female partners of childbearing potential and women female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. 9. Life expectancy ≥ 3 months. 10. Ability to understand the nature of this study and give written informed consent Exclusion Criteria: 1. Most recent chemotherapy ≤14 days and ≥Grade 1 chemotherapy-related side effects, with the exception of alopecia. 2. Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to initiation of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required. 3. Wide field radiotherapy (including therapeutic radioisotopes such as strontium-89 administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy. 4. Previous radiation delivered to the upper abdomen. 5. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement. 6. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. 7. Leptomeningeal metastases or spinal cord compression due to disease. 8. Pregnant or lactating. 9. Evidence of ascites, cirrhosis, portal hypertension, or thrombosis as determined by clinical or radiologic assessment. 10. History of abdominal fistula or gastrointestinal perforation ≤6 months prior to beginning study treatment. 11. Serious non-healing wound, active ulcer, or untreated bone fracture. 12. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and malabsorption syndrome). 13. Any of the following cardiac diseases currently or within the last 6 months: * Unstable angina pectoris * Congestive heart failure (NYHA ≥ Grade 2) * Conduction abnormality not controlled with pacemaker or medication * Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible) * Valvular disease with significant compromise in cardiac function 14. Inadequately controlled hypertension (i.e., systolic blood pressure \[SBP\] \>180 mmHg or diastolic blood pressure (DBP) \>100 mmHg) (patients with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment). 15. Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 16. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C. 17. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer. 18. Use of strong CYP34A inducers or inhibitors. 19. The herbal medications St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng will not be allowed during study treatment. Patients should stop using these herbal medications 7 days prior to first dose of study drug. 20. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 21. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.