Aims and Background: Irinotecan is a standard option for relapsed/refractory advanced colo- rectal cancer. Combination with raltitrexed and irinotecan at lower than MTD doses should preserve disease stabilisation while decreasing toxicity. Patients and Methods: From January 2004 to April 2009, we analyzed, retrospectively, our data on irinotecan + raltitrexed, fixed doses, as a second-line chemotherapy in elderly pa- tients (>70 years) with advanced colorectal can- cer after failure of oxaliplatin based chemothera- py twenty-three patients were evaluated. Iri- notecan 350 mg + raltitrexed 2.6 mg were given every 3 weeks. Tumo r measurements were ob- tained after every third course of therapy. Toxic- ity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, ver- sion 2. Results: The median number of treatment courses received per patient was 4 (range, 1 - 8). All pa-tients were assessable for toxicity and 21 for response. The most frequently observed severetoxicities were diarrhea (grade 2, 13%) No cases of significant neutropenia occurred. Ob- jective partial responses were observed in 3 pa- tients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time- to-progression of 4.3 months and a median sur- vival of 8.3 months. Conclusions: A three weekly irinotecan + raltitrexed administration can indu- ce tumor control in elderly patients with advanc- ed colorectalcancer that has progressed during or shortly after oxaliplatin-based chemotherapy. The diarrhea by irinotecan, seems mitigated by coad-ministration of a smaller dose of raltitrexed