Objective To observe the efficacy and safety of cetuximab chemotherapy combined with irinotecan in the treatment of advanced colorectal in the elderly.Methods 40 irinotecanresistant patients with K-Ras wild type were randomized to cetuximab weekly combined with irinotecan group (group A) and cetuximab biweekly combined with irinotecan group (group B).In group A,cetuximab was given at an initial dose of 400 mg/m2,followed by weekly 250 mg/m2.In group B,cetuximah and irinotecan were given at 500 mg/m2 and 180 mg/m2 respectively every two weeks.Time to progression (TTP),overall survival (OS) and toxicity were compared between the two groups.Results There were no significant differences in objective response rate (RR),disease control rate (DOC),TTP and OS between goup A and group B (30.0％ vs.25.0％,60.0％ vs.55.0％,5.8 months vs.5.6 months,9.8 months vs.9.5 months,respectively,all P＞0.05).Grade 3 or more toxicities including hematological toxicity,gastrointestinal reactions and skin toxicity were found in 2 cases,2 cases and 1 case respectively in group A and 3 cases,1 case and 2 cases respectively in group B.The two groups had no significant differences in toxicities (all P＞0.05).Conclusions Cetuximab combined with irinotecan therapy is effective in the treatment of advanced colorectal cancer in elderly irinotecan resistant patients.Cetuximab biweekly regimen is more convenient but has the same efficacy and toxicity as compared with cetuximab weekly regimen.