Abstract: Objective To investigate the efficacy and safety of raltitrexed／bevacizumab in combination with irinotecan or oxaliplation for advanced colorectal cancer as the second-line and second-line above treatment. Methods Fifteen cases of advanced colorectal cancer were enrolled to receive regimens including raltitrexed／bevacizumab combined with irinotecan or oxaliplation. Two cases were treated with raltitrexed+bevacizumab regimen，9 cases with raltitrexed+bevacizumab+irinotecan regimen，and 4 cases with raltitrexed+bevacizumab+oxaliplatin regimen. The doses of the drugs were as follows：bevacizumab 5mg／kg iv，d1；raltitrexed 2mg／m2 iv 15min，d2； irinotecan 180mg／m2 iv 1h，d2; and oxaliplatin 85mg／m2 iv 2h d2. Two weeks was a cycle for each regimen. Results The efficacy of the 15 patients could be evaluated. Two cases were in PR，10 cases in SD，3 cases in PD，the response rate was 13.3％， and the disease control rate was 80.0％. The median progress-free survival was 5.1 months（95％CI：3.4046.813 months），and the median overall survival was 11.5 months（95％CI：8.985-13.930 months）. The adverse effect included anorexia，nausea／vomiting，fatigue，leukopenia，thrombocytopenia，etc.，and the main 3-4 grade adverse effects were anorexia，nausea／vomiting， fatigue，and thrombocytopenia. Conclusion Raltitrexed／bevacizumab combined with irinotecan or oxaliplatin as the secondline and secondline above treatment for advanced colorectal cancer has high disease control rates， and the adverse effect is well tolerated. The combined regimen can be recommended as a phase Ⅲ clinical research and secondline and secondline above treatment for advanced colorectal cancer.