This is a single-arm, open-label, single-center prospective phase II study to evaluate the efficacy and safety of rechallenge chemotherapy in the third or later-line treatment in patients with advanced colorectal cancer. The primary end point is progression free survival (PFS). A total of 42 patients who failed with oxaliplatin, irinotecan and fluorouracil in previous treatment and could not receive the target therapy presently are planned for recruitment. For patients with metastatic colorectal cancer who met admission criteria, oxaliplatin- or irinotecan-based chemo regimen could be used and evaluation was repeated every 6 weeks. The treatment continues until the disease progression or the untolerable adverse reaction.

The treatment for reintroduction was oxaliplatin- or irinotecan-based chemo-regimen.

Optional chemotherapy regimen included XELOX,FOLFOX,FOLFIRI,Irinotecan single-agent

Inclusion Criteria

1. Patients age between 18 and 80 years
2. Histologically confirmed metastatic colorectal cancer (mCRC)
3. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
4. Treatment failure to at least two lines of chemotherapy (regimens should include oxaliplatin, fluorouracil and irinotecan); progression free survival (PFS) of prior oxaliplatin or irinotecan-based chemotherapy should be at least four months without any unrecoverable toxicity. Prior target therapy was acceptable
5. For those who received other anti-tumor treatment, the toxicity should have been restored, with the time interval from last dose of cytotoxic drugs, radiation or surgery (the wound should be healed completely) ≥3 weeks
6. Life expectancy≥12 weeks
7. At least one measurable lesion as defined by RECIST 1.1
8. Acceptable hematologic, hepatic, and renal function within 7 days from screening: the blood ANC count≥1.5*10^9/L; hemoglobin≥9.0 g/dl, the blood platelet count≥80 x 10^9/L, total bilirubin<1.5*upper limits of normal(ULN), ALT and AST<2.5*ULN(< 5 *ULN for patients with live metastasis), endogenous creatinine clearance rate>50ml/min
9. Targeted drugs are currently not suitable or affordable

Exclusion Criteria

1. Receiving other systemic anti-cancer treatment within 3 weeks
2. Prior radiation therapy of target measurable lesion
3. Presence of Grade III or IV chemo-related toxicity in previous treatment without recovery to Grade II or less
4. With other malignant tumor in 5 years; except for cured cervical carcinoma in situ or basal cell carcinoma
5. Symptomatic intracranial or meningeal metastasis
6. History of uncontrolled seizures, central nervous system dysfunction or mental disorder
7. Uncontrolled pleural or peritoneal effusion
8. Severe life-threatening concomitant disease that might impair the safety of patients or affect the completion of treatment, according to the researcher's judgment