127 Background: Oxaliplatin in association with fluoropyrimidines is universally considered one of the most effective drugs for colorectal cancer and the mainstay of front-line treatment of metastatic patients. In contrast the efficacy and safety profile of oxaliplatin based regimens in the late-care treatment space have been poorly and conflictingly reported. Methods: We identified a real-world cohort of metastatic colorectal cancer (mCRC) patients undergoing repeated oxaliplatin treatments in a single institution and retrospectively analysed their clinicopathological features to identify potential efficacy-predictive determinants of oxaliplatin response at retreatment (RETROX-CRC Study). Results: Out of 2,606 consecutive mCRC patients referred to Niguarda Cancer Center, 119 fulfilled the eligibility criteria of the study. The response rate (RR) and the disease control rate (DCR) after oxaliplatin retreatments were respectively 21.6% (95% CI 14.4-31.0%), and 57.8% (95% CI 47.7-67.4). A trend towards better RR and DCR was observed among patients who were exposed to oxaliplatin in the adjuvant setting, while a significantly poorer outcome was observed when two or more intervening treatments were delivered in between oxaliplatin exposures. Median progression-free survival (PFS) was 5.1 months (95% CI 4.3-6.1), significantly lower if oxaliplatin was re-administered beyond the third line (HR 2.02; 1.25-3.25; p=0.004). Safety data were reliably retrieved in 65 patients (54,6%). Of these 18.5% (12/65) and 7.7% (5/65) of them had G3-4 toxicities. Overall, toxicity was the cause of treatment discontinuation in almost a third of cases (28.6%; 34/119), with hypersensitivity reactions as the most prevalent reason for stopping treatment (58.8%; 20/34). Conclusions: In this large real-world series of 2,606 mCRC patients, less than 5% were re-treated with oxaliplatin. A late-disease control was achieved in almost 60% of patients, with a clinically acceptable sustained PFS and safety. Given the low performance of current standard drugs in late care of mCRC, retreatment with oxaliplatin might be considered a viable alternative especially if hopefully biology-based predictive markers for improving patient selection could be found.