Relapsed Mantle cell lymphoma (MCL) is often treated with Bruton's Tyrosine Kinase inhibitors (BTKi); however, post-BTKi relapse can be challenging. Adding venetoclax (VEN) to ibrutinib(IBR) has shown synergy in pre-clinical MCL models. Prior MCL studies of the combination report promising efficacy but have conducted limited dose finding. We sought to identify the optimal dosing combination, based on efficacy and toxicity, utilizing a continual re-assessment method of 6 combinations of IBR (280mg, 420 mg, and 560mg PO daily) and VEN (max dose of 200mg and 400mg PO daily). Eligible participants were not previously exposed to BTKi's and not high risk for Tumor Lysis Syndrome (TLS). VEN, initiated first at 100mg, then at 20mg PO daily after a TLS event, was started prior to adding IBR and ramped-up based on the dose level. Combination treatment continued for six 28 day cycles. 35 participants were enrolled and treated. One TLS event occurred with starting dose of 100mg VEN; no TLS was seen with 20mg. The optimal dosing combination was considered to be VEN 200mg and IBR 420mg with an ORR of 93.8% (95% CI: 73.6-99.7%) and DLT incidence of 6.2% (95% CI: 0.3-26.4%). Overall response for all arms was 82.3% (28/34; 95% CI: 65.5-93.2%) with a CR rate of 42.4% (14/33; 95% CI: 25.5-60.8%). A participant was not allocated to IBR 560mg and VEN 400mg. ORR benefit was not seen with higher dosing combinations and toxicity was higer; a comparison made within the limitations of small cohorts. Resistance was seen in nearly all arms. This trial was registered at www.clinicaltrials.gov #NCT02419560.