This study investigated 3D quantitative histogram assessment of diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI in the prediction of chemoradiotherapy (CRT) response in locally advanced rectal cancer. Histopathologic response assessment was centralised and defined according to AJCC tumour regression grade. A whole tumour histogram analysis and combined multiparametric scatterplots of ADC and Ktrans were used to assess tumour heterogeneity and prediction of CRT response. Post-CRT ADC 75th and 90th histogram quantiles were the most promising parameters for prediction of CRT response. However, DCE-MRI and multi-parametric scatterplots combining ADC and Ktrans did not add value in predicting response.