Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer

Inclusion Criteria: * Participants must have biopsy-proven diagnosis of a colorectal cancer with 1-4 liver metastases. There is no upper size limit and participants must have at least 800 mL of uninvolved liver. Liver metastases may be diagnosed by imaging alone, no liver biopsy is required. Extrahepatic disease is allowed if 1) it has been stable for 3 months prior to study entry, 2) the dominant disease burden is intrahepatic and 3) the patient is referred for definitive radiation therapy to the disease in the liver. * Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with spiral CT scan. See Section 13 for the evaluation of measurable disease. * Participants may have had prior chemotherapy, targeted biological therapy (i.e. sorafenib), surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as the prior therapy occurred more than 3 weeks before the first radiation treatment. Patients may not have had prior liver directed radiation, including radioembolization. * Participants must be 18 years of age or older. * Because no dosing or adverse event data are currently available on the use of high dose liver radiation in participants \<18 years of age, children are excluded from this study. * Expected survival must be greater than three months. * ECOG Performance Status 0 or 1.. * Participants must have liver metastases deemed unresectable due to anatomy, medical fitness, or presence of extrahepatic disease. * Participants must have normal organ and marrow function as defined below. History of transfusion is acceptable and transfusions may be given to meet eligibility requirements. * Hgb ≥ 9g/dL * Absolute neutrophil count ≥ 1,500/mm3 * Platelets ≥ 75,000/mm3 * Total bilirubin ≤ 1.5 X institutional upper limit of normal * AST (SGOT) and ALT (SGPT) ≤ 1.5 X institutional upper limit of normal * Creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 mL/min/1.73 m2 (Calculated per Cockroft \& Gault formula) for subjects with creatinine levels above institutional normal. * If patient has underlying cirrhosis, only Child-Pugh classification Group A patients should be included in this study. Clinical assessment of ascites and encephalopathy is required. Child-Pugh classification must be determined for all study participants at the time of eligibility analysis. As albumin and PT/INR are required for Child-Pugh classification; these labs should be drawn with other labs required for eligibility analysis. See Appendix B for Child-Pugh classification table. * The effects of radiation on the developing human fetus are known to be teratogenic and the safety of TAS-102 in pregnant women and their fetuses has not been established. Therefore, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after stopping study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document. * Ability to take oral medications (i.e. no feeding tube and able to swallow whole) Exclusion Criteria: * Women who are pregnant or lactating. Patients must be either surgically sterile (via hysterectomy or bilateral tubal ligation), post menopausal or using acceptable methods of contraception if they are of child bearing potential. Female patients of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to starting drug. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiation, breastfeeding should be discontinued if the mother is treated with radiation. * Participants with gross ascites or encephalopathy * Participants with local conditions or systemic illnesses that would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc. * Participants who have had prior liver directed radiation treatment, including selective internal radiation (SIRspheres or Theraspheres) * Participants with a serious medical illness that may limit survival to less than 3 months * Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. * Participants who are receiving any other investigational agents, or any other anti-cancer therapy during study treatment. * Participants with any uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or serious psychiatric illness/social situations that would limit compliance with study requirements. * Participants who have previously received TAS-102