Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma

Inclusion criteria: * Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinated process or body or tail. Diagnosis should be verified by local pathologist * cTNM stage: T1-4N0-2M0 * Confirmation of clinical and radiographic stage as borderline resectable (CT scan and/or MRI scan with contrast according to the NCCN criteria) by a multidisciplinary board, composed by a dedicated oncological surgeon, radiologist and GI oncologist) * Age \> 18 years old * No prior chemotherapy or radiation for pancreatic cancer * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * No grade ≥ 2 neuropathy * Laboratory parameters as follows: * Absolute neutrophil count (ANC) ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9 g/dL * Creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated GFR \>45 mL/min * Bilirubin ≤ 1.5 x ULN, including after adequate biliary stenting with metal stent (ideally 4 cm length) * Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5x ULN * CA 19.9 \< 2500 kU/l (baseline, prior to any therapy and absence of cholestasis) Exclusion Criteria: * Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI or PET scan), histologically proven or at laparoscopy, including distal nodal involvement beyond the peripancreatic tissues (including non-regional lymph node involvement, ie: proven involvement of precaval lumbar lymphadenopathy(ies) and/or distant metastases * Locally advanced disease as defined by the NCCN criteria (version 2.2021) ie \> 180° arterial encasement (SMA and CA) unreconstructible venous encasement (SMV/PV) due to tumor involvement or occlusion of a long segment. * CA 19.9 \> 2500 kU/l (baseline and absence of cholestasis) * Contraindication of surgery (general) * Contraindications to receive FFX or gemcitabine-nab-Paclitaxel * History of radiotherapy of the upper abdomen * Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabin * Patient \< 18 years old * Major surgery within 4 weeks of study entry * Uncontrolled pre-existing disease including, but not limited to: active infection, symptomatic congestive heart failure, unstable angina, social / psychiatric disorder that would limit compliance to treatment and good understanding of the informed consent form * Other concurrent anticancer therapies * Existence of another active neoplasia other than basal cell carcinoma of the skin, cervical carcinoma in situ or non-metastatic prostate cancer. Patients who have a history of neoplasia must have been in remission for more than 5 years to be included in the protocol * Pregnant or breastfeeding women; for women of childbearing potential only, a negative pregnancy test done \< 7 days prior to registration is required. Using of reliable contraception for at least 1 month before treatment is mandatory * Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study Additional exclusion criteria before randomisation: * Progressive disease (RECIST or PETCT, including non locoregional nodal involvement and increase of CA 19.9 by 20%) after receiving 4 cycles of FFX (or G/NP), including shift chemotherapy in case of early progression. * CA 19.9 \> 1000 kU/l after neoadjuvant therapy. * Presence of unmanageable toxicity during the first part of neoadjuvant chemotherapy (first 4 cycles or 6 doses of FFX or G/NP, respectively. * Pancreatic tumour \> 7.0 cm in greatest axial dimension at the time of randomization * Massive invasion of the stomach or intestines and/or direct intestinal invasion of the mucosae visible at ultrasoundendoscopy * Active gastric or duodenal ulcer disease at the time of randomization. Tolerated in case of antecedent without active ulcer (confirmation by endoscopy before iHD-SBRT)