ReviewUnderstanding the FOLFOXIRI-regimen to optimize treatment for metastatic colorectal cancer

•FOLFOXIRI plus bevacizumab represents a new standard option in mCRC patients.•Adequate schedules and early adverse event management are crucial for such treatment.•FOLFOXIRI plus anti-EGFRs showed promising results in clinical trials.•Novel surrogate end-points for FOLFOXIRI-based treatment are under investigation.•Predictive markers of efficacy are urgently needed to refine patients selection.

The management of metastatic colorectal cancer substantially improved over the last 10 years and median overall survival of patients might exceed 30 months. The selection of an effective first-line treatment represents a crucial point in order to achieve good outcome results. In the last years, the intensive FOLFOXIRI regimen in combination with bevacizumab became a new standard option in this setting. In the present review we summarized the main steps of FOLFOXIRI regimen development from the first pilot study to the recent findings with biological agents, with a specific focus on practical aspects, such as patient's selection, adverse event management, treatment schedules and post-progression strategies. Possible predictive markers, open issues and ongoing clinical trials have been also deeply described.