Diffusion-weighted MRI (DWI) may provide biologically relevant target volumes for dose-escalated radiotherapy in locally advanced rectal cancer (LARC). This planning study assessed the dosimetric feasibility of delivering hypofractionated boost treatment to intra-tumoural regions of restricted diffusion prior to conventional long-course radiotherapy. Ten patients previously treated with curative-intent standard long-course radiotherapy (50 Gy/25#) were re-planned. Boost target volumes ( ) were delineated semi-automatically using 40th centile intra-tumoural apparent diffusion coefficient value with expansions (anteroposterior 11 mm, transverse 7 mm, craniocaudal 13 mm). Biased-dosed combined plans consisted of a single-fraction volumetric modulated arc therapy flattening-filter-free (VMAT-FFF) boost (phase 1) of 5, 7, or 10 Gy before long-course VMAT (phase 2). Phase 1 plans were assessed with reference to stereotactic conformality and deliverability measures. Combined plans were evaluated with reference to standard long-course therapy dose constraints. Phase 1 BTV dose targets at 5/7/10 Gy were met in all instances. Conformality constraints were met with only 1 minor violation at 5 and 7 Gy. All phase 1 and combined phase 1 + 2 plans passed patient-specific quality assurance. Combined phase 1 + 2 plans generally met organ-at-risk dose constraints. Exceptions included high-dose spillage to bladder and large bowel, predominantly in cases where previously administered, clinically acceptable non-boosted plans also could not meet constraints. Targeted upfront LARC radiotherapy dose escalation to DWI-defined is feasible with appropriate patient selection and preparation. This is the first study to evaluate the feasibility of DWI-targeted upfront radiotherapy boost in LARC. This work will inform an upcoming clinical feasibility study.