The 6G vision for an open, distributed and user-centric evolution of the current SBA core network creates many security challenges and risks. The disaggregated heterogeneous cloud continuum (i.e. distributed cloud system with many stakeholders located in different regions, while private, public, or hybrid clouds are considered for the formation of the continuum), in conjunction with softwarization and IT-based infrastructure operations, set the stage for risks and challenges to trustworthiness in the 6G era. On top of the open and distributed 6G core over the edge-cloud continuum, SAFE-6G proposes a holistic research approach aimed to design, develop and validate a 6G-ready native trustworthiness framework by enabling user-centric safety, security, privacy, resilience, reliability functions. By utilizing (X)AI/ML techniques to cognitively coordinate and balance these functions, in order to optimize the Level of Trust (LoT), which realises the trust requirements and data governance policy that each user/tenant/human-role specifies, a feature that is considered an essential KVI for user-centric 6G. The proposed SAFE-6G framework covers the whole trustworthiness 6G lifecycle by applying trustworthiness analysis, realisation and post-evaluation during the whole user-centric service provision, from onboarding and deployment to operation and decomposition. Verification and validation of the proposed SAFE-6G framework will be performed at the Stream C SNS 6G-SANDBOX Athens platform using two Metaverse-based pilots. The immersive-applications will be tested considering different 6G system setups, different service flavors and deployments, under various threats and attacks.