The aim of this study was to determine the efficacy and safety of administering a combination of capecitabine and oxaliplatin in patients with advanced colorectal cancer, resistant to leucovorin/5-fluorouracil and irinotecan. Fifty-four patients with advanced colorectal cancer were prospectively evaluated (mean age 63 years, male/female 2:1) who had been previously treated with schemes containing fluoropyrimidines and irinotecan. All patients received oxaliplatin (130 mg/m2 as 2-hour intravenous infusion) the first day of the cycle and capecitabine (1000 mg/m2) twice daily, days 1-14. Cycles were repeated every 21 days until either disease progression or unacceptable toxicity. Patients were evaluated regarding their response to treatment every 9 weeks (toxicity was evaluated every 3 weeks). Total response rate was 28.3%. Median total survival was 13.5 months, and median time to progression was 5.3 months in a follow up of 24 months. Major adverse events were neutropenia, nausea, diarrhea, hand/foot syndrome, and neurotoxicity. No treatment-related or grade 4 toxicity-related deaths were observed. Additionally, no dosage decrease was required, and only 4 cycles were withheld for 1 week because of neutropenia. The combination of oxaliplatin and capecitabine is efficient and safe for patients with advanced colorectal cancer who have been previously treated with other therapeutic schemes. Furthermore, this is a convenient and well-tolerated scheme.