Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

Inclusion Criteria: 1. Male or female, 18 years of age or older, and of any ethnic or racial group. 2. Diagnosis of unresectable metastatic colorectal adenocarcinoma with liver-dominant bilobar disease. Diagnosis may be made by histo- or cyto-pathology, or by clinical and imaging criteria. 3. Disease progression or intolerance to at least two prior Food and Drug Administration-approved therapeutic regimens. 4. If extrahepatic disease is present, it must be asymptomatic. 5. If a primary tumor is in place, it must be asymptomatic. 6. Measurable target tumors using standard imaging techniques (RECIST v. 1.1 criteria). 7. Tumor replacement \< 50% of total liver volume. 8. Current Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 through screening to first treatment on study. 9. Completion of prior systemic therapy at least 14 days prior to enrollment. 10. Able to understand informed consent. Exclusion Criteria: 1. At risk of hepatic or renal failure * Serum creatinine \> 1.5 mg/dl * Serum bilirubin \> 1.3 mg/ml * Albumin \< 2.0 g/dL * Aspartate and/or alanine aminotransferase level \> 5 times upper normal limit * Any history of hepatic encephalopathy * Cirrhosis or portal hypertension * Clinically evident ascites (trace ascites on imaging is acceptable) 2. Contraindications to angiography and selective visceral catheterization * Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device) * Severe allergy or intolerance to contrast agents, narcotics, or sedatives that cannot be managed medically 3. Symptomatic lung disease 4. Prior therapy with Tas-102. 5. Contraindications to Tas-102 * Absolute neutrophil count \< 1,500/μl * Platelet count \< 75,000/μl * Allergy or intolerance to Tas-102 6. Unresolved toxicity of greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 2 due to prior therapies. 7. Evidence of potential delivery of * Greater than 30 Gy absorbed dose of radiation to the lungs during a single 90Y resin microsphere administration; or * Cumulative delivery of radiation to the lungs \> 50 Gy over multiple treatments. 8. Evidence of any detectable Tc-99m macro aggregated albumin flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow. 9. Previous radiation therapy to the lungs and/or to the upper abdomen 10. Any prior arterial liver-directed therapy, including chemoembolization, bland embolization, and 90Y radioembolization 11. Any intervention for, or compromise of the ampulla of Vater 12. Active uncontrolled infection. Presence of latent or medication-controlled HIV and/or viral hepatitis is allowed. 13. Significant extrahepatic disease * Symptomatic extrahepatic disease (including primary tumor, if unresected). * Greater than 10 pulmonary nodules (each \< 20 mm in diameter) or combined diameter of all pulmonary nodules \> 15 cm. * Peritoneal carcinomatosis 14. Life expectancy less than 3 months 15. Pregnant or lactating female 16. In the investigator's judgment, any co-morbid disease or condition that would place the patient at undue risk and preclude safe use of radioembolization or Tas-102.