PI-RADS score 3 is recognized as equivocal likelihood of clinically significant prostate cancer (csPCa) occurrence. We aimed to develop a Radiomics machine learning (RML)-based redefining score to screen out csPCa in equivocal PI-RADS score 3 category.Total of 263 patients with the dominant index lesion scored PI-RADS 3 who underwent biopsy and/or follow-up formed the primary cohort. One-step RML (RML-i) model integrated radiomic features of T2WI, DWI, and ADC images all together, and two-step RML (RML-ii) model integrated the three independent radiomic signatures from T2WI (T2WIRS), DWI (DWIRS), and ADC (ADCRS) separately into a regression model. The two RML models, as well as T2WIRS, DWIRS, and ADCRS, were compared using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analysis (DCA). Two radiologists were asked to give a subjective binary assessment, and Cohen's kappa statistics were calculated.A total of 59/263 (22.4%) csPCa were identified. Inter-reader agreement was moderate (Kappa = 0.435). The AUC of RML-i (0.89; 95% CI 0.88-0.90) is higher (p = 0.003) than that of RML-ii (0.87; 95% CI 0.86-0.88). The DCA demonstrated that the RML-i and RML-ii significantly improved risk prediction at threshold probabilities of csPCa at 20% to 80% compared with doing-none or doing-all by PI-RADS score 3 or stratifying by separated DWIRS, ADCRS, or T2WIRS.Our RML models have the potential to predict csPCa in PI-RADS score 3 lesions, thus can inform the decision making process of biopsy.