Abstract: Objective To observe the clinical efficacy and adverse reactions of oxaliplatin combined with S-1 plus bevacizumab regimen in the treatment of advanced colorectal cancer. Methods We made a retrospective analysis of hospitalized 47 cases of advanced colorectal cancer diagnosed pathologically from Jun 2010 to Jun 2012, and divided them into two groups, the study group received oxaliplatin combined with S-1 plus bevacizumab regimen (n=22) and the control group received oxaliplatin combined with S-1 regimen only (n=25). The efficacy and side effects of two groups were observed and compared. Results The objective response rates were 63.6% in the study group and 36.0% in control group, and the disease control rates were 86.4% and 68.0% (P>0.05), the median progression-free survival time were 7.3 and 4.8 months (P<0.05), and the median overall survival time were 15.0 and 12.6 months (P<0.05). The increased adverse reactions in the study group included hypertension and bleeding, with the incidence rates of 9.1% and 4.5%, respectively, however, as all were of Grade I and Ⅱ, they could be controlled after drug treatment and did not affect the continuity of chemotherapy. Conclusion Oxaliplatin combined with S-1 plus bevacizumab regimen could improve the clinical efficacy of advanced colorectal cancer, prolong the survival time and has good tolerance in the patients. Therefore, it has promising prospects in clinical application.