Abstract: Objective To compare the efficacy and safety between biweekly raltitrexed and irinotecan with FOLFIRI for patients with metastatic colorectal cancer.Methods A total of 50 patients with metastatic colorectal carcinoma were included into the study. There were 25 patients for irinotecan plus raltitrexed regimen group（treatment group： raltitrexed 2.5mg／m² iv d₁， irinotecan 180mg／m² iv d₁） and 25 patients for FOLFIRI group（control group： irinotecan 180mg／m² iv d₁, leucovorin 400mg／m² iv d₁， fluorouracil 400mg／m² iv d₁， fluorouracil 2400mg／m² iv 46-48 h）. Both two regimens were 14 days as a cycle，and a total of 12 cycles was applied unless there was evidence of disease progression or intolerance of treatment. The efficacy was evaluated every 3-cycle chemotherapy and side effects were evaluated every cycle. Results Patients in treatment group received 1 CR， 4 PR， 18 SD， 2 PD； and in control group were 2 PR， 19 SD， 4 PD. No statistical difference was found between two groups in regard to response rate（20％ vs. 8％） and disease control rate（92％ vs. 84％）. Raltitrexed and irinotecan regimen had higher frequency of grade 1-2 transaminase increase（24％ vs. 4％，P＜0.05）， while FOLFIRIF regimen had higher frequency of grade 1-2 neutropenia（48％ vs. 20％， P＜0.05） and mucositis（32％ vs. 8％， P＜0.05）. Conclusion Raltitrexed and irinotican regimen is effective for metastatic colorectal cancer. It has lower toxicity compared with FOLFIRI regimen.