For patients resistant to leucovorin (LV) and 5-fluorouracil (5-FU), the addition of oxaliplatin (85 or 100mg/m²) to bimonthly LV–5-FU has given a response rate of 20–46%. The highest response rate has been observed with oxaliplatin 100mg/m² (FOLFOX2). The present phase II study (FOLFOX6) infused oxaliplatin (100mg/m²) with LV (400mg/m²) as a 2-h infusion on day 1, followed by bolus 400mg/m² and a 46-h infusion (2.4–3g/m²) of 5-FU, every 2 weeks. Among the 60 patients treated, 16 (27%) had partial responses (95% confidence interval: 15–38), 27 (45%) had stable disease, 15 (25%) experienced disease progression and 2 (3%) had non-measurable disease. From the start of FOLFOX6, median progression-free survival was 5.3 months and median survival 10.8 months. From the 448 cycles analysed, NCI-CTC grade 3–4 toxicities per patient were: peripheral neuropathy 16%, nausea 7%, diarrhoea 7%, mucositis 5%, neutropenia 24%, thrombocytopenia 2%. Overall 26 (46%) patients experienced grade 3–4 toxicities. Because of toxicity, only 36% of the patients received ≥90% of the scheduled oxaliplatin dose intensity. FOLFOX6 was active in pretreated patients resistant to LV–5-FU and is being investigated as first-line therapy. We are now investigating FOLFOX7, a regimen with a higher oxaliplatin dose intensity and a lower 5-FU dose.