Primary Endpoint : To evaluate the Disease control rate (DCR)

Secondary Endpoints:

To evaluate the Progression-free survival (PFS), Overall survival(OS) and Safety profile

70 Per-protocol patients Plan to recruit 70 evaluable patients (With expected dropout rate of 22%, the sample size would be 90 subjects.) Simon's two-stage design (Simon, 1989) will be used. The null hypothesis that the true response rate is 0.45 will be tested against a one-sided alternative. In the first stage, 42 patients will be accrued. If there are 19 or fewer responses in these 42 patients, the study will be stopped. Otherwise, 28 additional patients will be accrued for a total of 70. The null hypothesis will be rejected if 39 or more responses are observed in 70 patients. This design yields a type I error rate of 0.05 and power of 0.8 when the true response rate is 0.6.

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the metastatic colorectal cancer;
2. Previously treated with fluorouracil-, oxaliplatin-, and irinotecan-based chemotherapy, and anti-vascular endothelial growth factor (anti-VEGF) biological therapy;
3. The RAS wild-type patients need to receive anti-EGFR therapy;
4. Presence of at least one measurable tumor lesion which is defined as lesion that can be measured in at least one dimension (longest diameter) with a minimum size of : 10mm by CT scan, MRI and PET-CT(no less than double the slice thickness and a minimum of 10mm)(according to RECIST guideline version 1.1);
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2;
6. Investigators prescribe Lonsurf® for metastatic colorectal cancer patients who had prior treatment with Anti-VEGF and Anti-EGFR agent on routine basis. Depending on RAS status, patients with RAS mutant receive Lonsurf® as 3rd line treatment, those with RAS wild type receive Lonsurf® as 3rd/4th line treatment;
7. Patients received either oxaliplatin or irinotecan.

Exclusion Criteria:

1. Patients previously received Lonsurf® (Trifluridine／Tipiracil) or regorafenib;
2. With active central nervous system (CNS) metastasis (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth);
3. With clinically significant gastrointestinal hemorrhage;
4. Previous or current systemic malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ, unless there has been a disease-free interval of at least 5 years;
5. The patient at high risk from treatment complications including but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia, uncontrolled diabetes, liver or renal failure and psychiatric illness or social situation that would preclude study compliance;
6. Active infection.