Background: Although a variety of FOLFOX regimens (5-fluorouracil and L-leucovorin combined with oxaliplatin) are widely used for the treatment of advanced colorectal cancer, the neurotoxicity caused by oxaliplatin is often problematic. The aim of this observational study was to assess the safety and efficacy of a modified version of the FOLFOX6 regimen (mFOLFOX6) when administered using the 'stop-and-go' strategy. Patients and Methods: A total of 112 eligible patients treated between June 2005 and July 2007 were identified using the prospective cohort database system of Kyoto University Hospital. Results: The median follow-up was 16.3 months (range 1.6-33.9), and the response rate was 33.3% (95% CI 14.5-52.2), 40.0% (95% CI 22.5-57.5) and 14.0% (95% CI 3.6-24.3) for patients who received mFOLFOX6 as first-line therapy, second-line therapy and third-or later-line therapy, respectively. The estimated median progression-free survival was 8.7 months (95% CI 2.3-15.1) and 8.2 months (95% CI 7.3-9.1) for patients on first-line and second-line therapy, respectively. The median overall survival was not reached as of April 2008 for the patients on first-line therapy, while it was 27.1 months (95% CI 22.0-32.2) for those on second-line therapy. Severe neurotoxicity occurred in only 4 patients (3.6%). Conclusion: mFOLFOX6 administered using the stop-and-go strategy significantly reduced oxaliplatin-induced neurotoxicity relative to conventional FOLFOX treatment, without compromising efficacy. Copyright (C) 2008 S. Karger AG, Basel.