Two consecutive studies have evaluated the efficacy of oxaliplatin combined with the Nordic bolus schedule of 5-fluorouracil and folinic acid as first-line treatment in metastatic non-resectable colorectal cancer. One hundred and twelve patients were followed after end of first-line treatment and any secondary therapy registered. Fifty-three patients (47%) did not receive second-line irinotecan-based chemotherapy. The main reason was too poor performance status (59%). These patients had a median survival of only 1.7 months after progression of first-line therapy. The best predictive factors at start of first-line chemotherapy for receiving later second-line chemotherapy were performance status and alkaline phosphatase level. Fifty-nine patients (53%) received irinotecan-based second-line therapy. Four (7%) patients had a partial response, and 28 (52%) had stable disease. Median progression-free survival after second-line chemotherapy was 4.1 months and median survival 9.5 months. Median survival after first-line chemotherapy and secondary liver surgery was 34 months and five-year disease-free survival 8%. Survival among patients receiving both first- and second-line chemotherapy was 20.8 months, but only 8.9 months in patients not receiving second-line irinotecan-based chemotherapy. Poor performance status or elevated alkaline phosphatase level at start of first-line chemotherapy predicts whether second-line chemotherapy will be given or not.