The efficacy of oxaliplatin combined with high-dose 5-fluorouracil (5-FU) and folinic acid (FA) as an outpatient salvage treatment for patients with metastasized colorectal cancer was retrospectively analyzed in one center. Tumor progression had occurred for the majority of patients during two regimens (n = 11) otherwise during one (n = 1) regimen of prior 5-FU-based chemotherapy, which had been applied in a standardized sequential fashion. As third-line therapy oxaliplatin was infused intravenously over 2 h at a dose of 60 mg/m2 prior to a 2-h infusion of FA (500 mg/m2). 5-FU (2,600 mg/m2) was subsequently given over 24 h. A favorable response was observed in 9/12 (75%) of the heavily pretreated patients, including partial remissions in 3/12, minor responses in 2/12 and stable disease in 4/12 patients. The median progression free time was 23 weeks (interquartile range i. r. 0-28) for all patients, the median survival time from start of third-line therapy 55 weeks (i. r. 40-86). The median survival time from the beginning of first-line palliative chemotherapy was 34 months (i. r. 25-45 months). The highest toxicity was WHO grade III and was observed in six patients: Nausea (2), diarrhea (3), vomiting (2) and peripheral neuropathy (1). The quality of life was not adversely affected by the oxaliplatin/5-FU/FA-regimen as assessed by the EORTC QLQ-C30 questionnaire. Thus, the results show the efficiency and low toxicity of oxaliplatin/high-dose 5-FU/FA as palliative third-line therapy of patients with metastasized colorectal cancer and emphasize that sequential palliative chemotherapy may lead to extended survival of these patients.