Background: Coronary vasospasm associated with 5-FU based chemotherapy regimens is well described in the literature and has been reported to occur more often with infusional 5-FU or capecitabine than with bolus 5-FU. Patients suffering from fluoropyrimidine (FP) induced vasospasm have been successfully treated with bolus 5-FU based regimens. Given the additional benefit of oxaliplatin in the management of patients with early and advanced colorectal cancer, retaining oxaliplatin in the treatment regimens is desirable. We performed a retrospective review to explore the safety of substituting FLOX (bolus 5-FU, oxaliplatin, leucovorin) or IFL (irinotecan, bolus 5-FU and leucovorin) for FOLFOX (infusional 5-FU , oxaliplatin and leucovorin) and CAPOX (capecitabine and oxaliplatin) in patients with FP-induced coronary vasospasm. Methods: The pharmacy database at Mayo Clinic was queried to identify patients who developed coronary vasospasm associated with FOLFOX or CAPOX between January, 2011 and January, 2018. Information on adverse effects of FLOX and IFL regimens was obtained. Results: 11 patients (median age 54 years, range 36-77, 3 males and 8 females) developed 5-FU induced vasospasm, 10 with FOLFOX and 1 with CAPOX, 7 in adjuvant setting and 4 in metastatic setting. In 10 out of 11 patients, chest pain was the presenting complaint which started within 48 hours of beginning of 5-FU infusion. In 9 out of 11 patients, vasospastic event occurred after first cycle of chemotherapy. All patients made full recovery after discontinuation of infusional 5-FU or capecitabine. Of the11 patients, 10 subsequently received FLOX with median total bolus 5-FU doses of 7 (range 2-22), 7 days to 18 months after the event including 7 patients within 4 weeks of the event. FLOX did not cause any cardiovascular adverse events in any of the 10 patients. One patient received IFL about 51 months after initial exposure to FOLFOX and tolerated the regimen well. Conclusions: Bolus 5-FU based regimens such as FLOX are safe in patients who have experienced coronary vasospasm with infusional 5 FU or capecitabine.